Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.

BACKGROUND: In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD. METHODS: Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded. RESULTS: Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children under 2 years and 9 for those 2 years old and over. CONCLUSIONS: This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist.

Not just a chalazion-focal eyelid and orbital infection with Saksaenea vasiformis in an immunocompetent child.

We present the case of a 2-year-old immunocompetent boy who presented with subacute right-sided orbital cellulitis due to Saksaenea vasiformis infection. Initial differential diagnoses included chalazion and localized soft tissue malignancy. There was no history of trauma. Immunological review and investigations were unremarkable. He was treated with a total of 3 months of antifungal therapy. Following resolution, he had two episodes of spontaneously resolving localized eyelid erythema at 2 and 8 months.

Examining the interseasonal resurgence of respiratory syncytial virus in Western Australia.

BACKGROUND: Following a relative absence in winter 2020, a large resurgence of respiratory syncytial virus (RSV) detections occurred during the 2020/2021 summer in Western Australia. This seasonal shift was linked to SARS-CoV-2 public health measures. We examine the epidemiology and RSV testing of respiratory-coded admissions, and compare clinical phenotype of RSV-positive admissions between 2019 and 2020. METHOD: At a single tertiary paediatric centre, International Classification of Diseases, 10th edition Australian Modification-coded respiratory admissions longer than 12 hours were combined with laboratory data from 1 January 2019 to 31 December 2020. Data were grouped into bronchiolitis, other acute lower respiratory infection (OALRI) and wheeze, to assess RSV testing practices. For RSV-positive admissions, demographics and clinical features were compared between 2019 and 2020. RESULTS: RSV-positive admissions peaked in early summer 2020, following an absent winter season. Testing was higher in 2020: bronchiolitis, 94.8% vs 89.2% (p=0.01); OALRI, 88.6% vs 82.6% (p=0.02); and wheeze, 62.8% vs 25.5% (p<0.001). The 2020 peak month, December, contributed almost 75% of RSV-positive admissions, 2.5 times the 2019 peak. The median age in 2020 was twice that observed in 2019 (16.4 vs 8.1 months, p<0.001). The proportion of RSV-positive OALRI admissions was greater in 2020 (32.6% vs 24.9%, p=0.01). There were no clinically meaningful differences in length of stay or disease severity. INTERPRETATION: The 2020 RSV season was in summer, with a larger than expected peak. There was an increase in RSV-positive non-bronchiolitis admissions, consistent with infection in older RSV-naïve children. This resurgence raises concern for regions experiencing longer and more stringent SARS-CoV-2 public health measures.

Changing Epidemiology and Predisposing Factors for Invasive Pneumococcal Disease at Two Australian Tertiary Hospitals.

BACKGROUND: Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality in children. Universal pneumococcal conjugate vaccination has changed the epidemiology of IPD. In vaccinated children, IPD can be a marker of an underlying immunodeficiency. METHODS: This is a retrospective audit of children younger than 18 years with IPD admitted to 2 tertiary pediatric hospitals in Australia between 2011 and 2017. Data on predisposing conditions, immunologic evaluation, pneumococcal serotype, antibiotic susceptibility and treatment were collected. RESULTS: During the 7-year period, there were 131 presentations with IPD in 127 children; 3 children had recurrent IPD. Patients presented with sepsis (41%), empyema (29%), meningitis (18%), mastoiditis (12%), pneumonia (10%) and septic arthritis (4%). In 19 (15%) presentations, risk factors for IPD were present, including malignancy, hematologic disorder, chronic liver disease, chronic kidney disease and cochlear implant. Pneumococcal serotypes were determined in 78/131 (60%) of presentations: the most frequent serotypes were 19A (19%), 3 (13%), 7F (10%) and 19F (8%) and non-vaccine serotypes 22F (8%), 35B (6%), 15A (4%) and 38 (4%). Overall, 11% of isolates were non-susceptible to ceftriaxone. Only 36 patients (32%) had an immunologic evaluation, and 4 patients had proven or probable immunodeficiency. CONCLUSION: Although pneumococcal conjugate vaccine serotypes 19A, 3, 19F and 7F remain frequent causes of IPD, non-vaccine serotypes are emerging. Our data support vancomycin treatment for children with pneumococcal meningitis given 11% of our isolates were not susceptible to ceftriaxone. It is important to consider underlying conditions predisposing to IPD in a population with high rates of pneumococcal vaccination.

Prevalence of Immunodeficiency in Children With Invasive Pneumococcal Disease in the Pneumococcal Vaccine Era: A Systematic Review.

IMPORTANCE: Despite increasing access to vaccination, invasive pneumococcal disease (IPD) is responsible for approximately 826 000 deaths worldwide in children younger than 5 years each year. To allow early identification and prevention, an improved understanding of risk factors for IPD is needed. OBJECTIVES: To review the literature on the prevalence of primary immunodeficiency (PID) in children younger than 18 years presenting with IPD without another predisposing condition and to inform guidelines for immunologic evaluation after the first episode of IPD based on published evidence. EVIDENCE REVIEW: A literature search of PubMed, Embase (inception [1974] to February 28, 2019), and MEDLINE (inception [1946] to February 28, 2019) was conducted using the terms Streptococcus pneumonia, Streptococcus pneumoniae, pneumococcal infection, Streptococcus infection, pneumococcal meningitis, immunodeficiency, immune response, immunocompromised, susceptib*, precursor, predispose*, recurren*, newborn, neonat*, infan*, toddler, child, preschooler, adolescen*, and pediatric. Publications reporting original data on immunodeficiency in children with microbiologically confirmed primary or recurrent IPD were included. Strength of clinical data was graded according to the 5-point scale of the Oxford Centre for Evidence-Based Medicine. FINDINGS: In 6022 unique children with primary IPD, 5 of 393 (1.3%) to 17 of 162 (10.5%) of all children and 14 of 53 (26.4%) of those older than 2 years had a PID identified. Higher rates of PID, up to 10 of 15 (66.7%), were found in children with recurrent IPD. Antibody deficiency was the most common immunodeficiency, followed by complement deficiency, asplenia, and rarer defects in T-cell signaling. The site of infection was a key indicator for the risk of underlying PID, with the greatest risk of PID in children with meningitis or complicated pneumonia. CONCLUSIONS AND RELEVANCE: Results of this study suggest that invasive pneumococcal disease, and particularly recurrent IPD, is an important marker of underlying PID in children without other risk factors. The findings also suggest that children older than 2 years with pneumococcal meningitis or complicated pneumonia and all children with recurrent IPD should be referred for an immune evaluation. TRIAL REGISTRATION: PROSPERO identifier: CRD42017075978.

Treatment Options for Resistant Kawasaki Disease.

"Resistant" Kawasaki disease is defined by the American Heart Association as failure to respond within 36 h following the first dose of intravenous immunoglobulin. The optimal management of resistant Kawasaki disease remains uncertain, the outcomes are potentially serious, and the cost of some treatments is considerable. We review the current evidence to guide treatment of resistant Kawasaki disease. Given the relative rarity, there are few trial data, and studies tend to be small and methodologically heterogeneous, making interpretation difficult and limiting generalisability. The literature on resistant Kawasaki disease should be interpreted with reference to current expert consensus guidelines.

The long shadow of lemierre's syndrome.

Lemierre's syndrome is a rare and feared complication of pharyngitis, occurring most commonly in adolescents and young adults. It is typically defined by the constellation of septic internal jugular vein thrombophlebitis, pulmonary and other septic emboli, and sterilesite infection by Fusobacterium necrophorum. The rarity and severity of Lemierre's syndrome has made it an attractive subject for case reports but there is a paucity of evidence to inform areas of persistent uncertainty. In recent years, heightened attention and controversy has focused upon speculation that a purported rise in the incidence of Lemierre's syndrome is due to reduced antibiotic prescribing for respiratory tract infections, that F. necrophorum is an under-appreciated cause of acute tonsillopharyngitis and that testing and targeted treatment would prevent cases of Lemierre's syndrome.

Kawasaki disease and immunisation: A systematic review.

BACKGROUND: Kawasaki disease is a complex and potentially serious condition. It has been observed in temporal relation to immunisation. METHODS: We conducted a systematic literature review using various reference sources to review the available evidence published in the literature. RESULTS: We identified twenty seven publications reporting a temporal association between immunisation and Kawasaki disease. We present a systematic review of data drawn from randomised controlled trials, observational studies, case series and reports, and reviews. Overall there was a lack of standardised case definitions, making data interpretation and comparability challenging. CONCLUSIONS: Although a temporal relationship between immunisation and Kawasaki disease is suggested, evidence for an increased risk or a causal association is lacking. Implementation of a standardised Kawasaki disease case definition would increase confidence in the findings and add value to future studies of pre- or post-licensure vaccine safety studies.